The past, present and future perspectives of matrix metalloproteinase inhibitors

Kang Li, Franklin R. Tay, Cynthia Kar Yung Yiu

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for inhibition when homeostasis breaks down in the ECM. There are 4 generations of MMP inhibitors (MMPIs), ranging from small molecules or peptides to antibodies and protein-engineered inhibitors of metalloproteinase. Although a plethora of MMPIs has been synthesized, most of them have failed in clinical trials or are still in the laboratory stage of development. The present review summarizes the development of MMPIs, their associated problems and discusses future directions for the development of the future generations of MMPIs.

Original languageEnglish (US)
Article number107465
JournalPharmacology and Therapeutics
Volume207
DOIs
StatePublished - Mar 2020

Keywords

  • Inhibitor
  • MMP
  • MMPI
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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